Coatings have long been applied to pharmaceuticals, animal health products, and food products for various reasons, including masking unpleasant taste, protecting components from degradation, controlling the site of drug release (enteric coating), controlling the absorption of the drug compound by retarding release of the drug from the dosage form, improving the appearance of the product, and changing the physical surface characteristics of the ingredients.
The oldest method of coating is perhaps sugar-coating. In sugar coating, the objects to be coated are moistened with an aqueous sugar solution and tumbled (for example in a rotating pan), and then dried. The moistening and drying procedures are generally repeated many times before satisfactory protection of the object to be coated and a smooth surface are obtained.
It is generally considered desirable to apply a seal coat directly over the uncoated tablet, etc. in order to separate the object to be coated from the water that is used in the coating process. Many substances have been used as sealing agents in this step, including cellulose-acetate-phthalate, zein, shellac, and other specific resins. Thereafter, the product may be subcoated, syrup coated, finished, and polished, although many variations of these procedures are used. The sealing coat is applied as a dilute, nonaqueous solution, and not more than two or three thin coats are used to seal the tablets.
More recently, film-coating techniques that have used a wide variety of materials of coating agents have been developed, in order to overcome the host of problems that can be encountered in attempting to sugar coat a tablet, such as color spotting, cracking of the coating, degradation of the drug in the tablet, and excessive subcoatings which cause retardation of disintegration and bioavailability.
Most film-coats are prepared by depositing one or more film-forming polymers onto the object to be coated, resulting in coatings that represent usually from about 2 to 10% by weight of the coated tablet. Such film coatings tend to have better resistance to chipping of the coating, increased tablet strength, and decreased production cost as compared to sugar coating. The polymers used in film-coating are generally water soluble or water dispersible cellulose derivatives such as hydroxypropyl methylcellulose and carboxymethylcellulose.
Hydrophobic polymers such as certain cellulose derivatives, acrylic resins, waxes, higher aliphatic alcohols, and polylactic polyglycolic acids have been used in the development of controlled release pharmaceutical dosage forms, such as tablets, capsules, suppositories, spheroids, beads or microspheres by, e.g., overcoating the individual dosage units with these hydrophobic polymers.
It is known in the prior art that these hydrophobic coatings can be applied either from a solution, suspension or as dry powders. Since most of these polymers have a low solubility in water, they are usually applied by dissolving the polymer in an organic solvent and spraying the solution onto the individual drug forms (such as beads or tablets) and evaporating off the solvent.
The use of organic solvents in the preparation of polymer coatings is considered problematic as the formulations have inherent problems with regard to flammability, carcinogenicity, and safety in general. In addition, the use of organic solvents is not favored due to environmental concerns.
Most commercially available aqueous dispersions of pre-formed polymers (e.g., ethylcellulose-Aquacoat.RTM., Surelease.RTM.) are prepared via emulsification of organic polymer solutions or polymer melts into an aqueous phase followed by homogenization. Organic solvents used in this process are water-immiscible.
While coatings for pharmaceutical formulations, etc., comprising zein are considered desirable, the use of such coatings has been limited because zein is not soluble in water-immiscible organic solvents and therefore cannot be prepared by the traditional emulsification techniques described above.
With regard to confectionery coatings, U.S. Pat. No. 2,791,509 (Cosler) describes a coating for non-cereal confectionery articles which comprises zein and acetylated glycerides which are applied to the food articles in an edible organic solvent vehicle, such as 90% ethanol, or ethanol denatured with a minor amount of ethyl acetate. However, it is stated therein that virtually any organic solvent can be used which is edible, nontoxic, and in which the zein and acetylated monoglyceride are soluble. The coating is said to form a continuous barrier against the penetration of water into the confectionery and against penetration of fat, oil and moisture from the interior of the confectionery to the outside.
U.S. Pat. No. 4,931,295 (Courtright, et al.) is related to methods for producing a chewing gum with a zein coated "delayed release" high-potency sweetener. The term "delayed release" as used therein is intended to infer a delayed release of the high-potency sweetener during chewing of the gum and during storage. In this process, the zein is mixed with a solvent for the zein, and a water soluble modified cellulose compound such as HPMC to form a modified zein solution. This modified zein solution is applied to a high-potency sweetener and then dried to produce the delayed release sweetener particles. The particles are then added to a chewing gum formulation. In a preferred embodiment, the zein is dissolved in water having a pH of between about 11.5 and about 12.1 and contains about 13 weight percent zein. The zein is said to be either completely dissolved or a major portion of the zein is dissolved and a minor portion is suspended in the water. In a second preferred method, the zein is dissolved in ethanol, to between about 10-15% by weight of the solution. The zein is said to comprise about 1-15% of the coated high-potency sweetener, the zein, and the HPMC.
U.S. Pat. No. 3,371,015 (Sjogren, et al.) describes tablet coatings comprising an inner layer of a polyethylene glycol which is soluble in water and in certain organic solvents, and an outer layer of a film-forming thermoplastic substance which is water-insoluble but soluble in volatile organic solvents. Substances which are considered to be suitable for the outer layer include cellulose acetates, acrylic resins, silicone resins, as well as shellac and zein.
U.S. Pat. No. 3,365,365 (Butler, et al.) describes pharmaceutical compositions in the form of beadlets suitable for filling into hard shell capsules, wherein the beadlets are enteric coated with a coating containing zein and an abietic acid type rosin. The enteric coating which is used for preparing chlordiazepoxide beadlets are produced by mixing the abietic acid type rosin with zein, a wetting agent, an anhydrous lower aliphatic alcohol, and a plasticizer.
U.S. Pat. No. 3,370,054 (Loew) describes deaminated zein dispersible in solutions having a pH of at least 6.5 which is prepared by hydrolyzing zein with strong alkalies, and thereafter removing the alkali by precipitation.
U.S. Pat. No. 4,983,403 (Ardaillon, et al.) describes a biologically active substance for the feeding of ruminants. The composition consists of a ruminant feed additive coated with a mixture consisting of zein in combination with a non-water-soluble polymer; a hydrophobic substance; a non-water-soluble polymer and a plasticizing agent; or a hydrophobic substance and a non-water-soluble polymer. The coating mixture is said to be obtained by dispersing or dissolving zein in a solution or dispersion of the non-water-soluble polymer and/or of the hydrophobic substance, and optionally, the plasticizing agent, in an organic solvent or in a mixture of suitable organic solvents. The coating mixture is obtained after evaporation of the solvent or solvents.